Association of variation at the ABO locus with circulating levels of sICAM-1, sP-selectin and sE-selectin: a Meta-Analysis.

Background—Circulating levels of soluble intercellular adhesion molecule-1, soluble P-selectin, and soluble E-selectin have been associated with variation at the ABO locus. To evaluate these associations and the effect sizes, we performed a meta-analysis with new and previous reported data for polymorphism rs579459. Methods and Results—Compared with major allele homozygotes, heterozygotes and minor allele homozygotes had 4.6% (95% CI, 3.4%–5.8%, P=7.3×10−14) and 7.2% (95% CI, 4.7%–9.7%, P=1.5×10−8), respectively, lower soluble intercellular adhesion molecule-1 levels (n=33 671). An allele dose-dependent association also was observed for soluble P-selectin (n=4921) with heterozygotes and minor allele homozygotes having 11.5% (95% CI, 7.2%–15.8%, P=1.7×10−7) and 18.6% (95% CI, 9.1%–28.1%, P=1.2×10−4), respectively, lower levels than in major allele homozygotes. A larger effect size, again consistent with an additive genetic model, was seen for soluble E-selectin (n=2860) whose level was 25.6% (95% CI, 19.0%–32.2%, P=2.1×10−14) lower in heterozygotes and 43.3% (95% CI, 36.9%–49.3%, P=4.3×10−42) lower in minor allele homozygotes than in major allele homozygotes. Conclusions—The data support the association of variation at the ABO locus with soluble intercellular adhesion molecule-1, soluble P-selectin, and soluble E-selectin levels.